Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial.

BACKGROUND: Opioid/acetaminophen (APAP) combination analgesics are widely prescribed for the relief of moderate pain. Tramadol is a synthetic analgesic that has been shown to be effective both alone and in combination with APAP. OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability of tramadol/APAP tablets with codeine/APAP capsules. METHODS: This 4-week, randomized, double-blind, parallel-group, active-control, double-dummy, multicenter trial compared tramadol/APAP (37.5 mg/325 mg) with codeine/APAP (30 mg/300 mg) for the management of chronic nonmalignant low back pain, osteoarthritis (OA) pain, or both in adults. Pain relief (scale, 0 = none to 4 = complete) and pain intensity (scale, 0 = none to 3 = severe) were measured 30 minutes and then hourly for 6 hours after the first daily dose each week. Patients and investigators assessed the efficacy (scale, 1 = poor to 5 = excellent) of each medication, and patients recorded daily doses of study and rescue medications. RESULTS: A total of 462 patients (mean age, 57.6 years) were randomly assigned to treatment, with 112 (24%) reporting chronic low back pain, 162 (35%) reporting OA pain, and 188 (41%) reporting both low back and OA pain; 309 patients (67%) received tramadol/APAP and 153 (33%) received codeine/APAP. Pain relief and changes in pain intensity were comparable from day 1, as early as 30 minutes after the first dose, and lasted for at least 6 hours. Total pain relief scores (11.9 for tramadol/APAP; 11.4 for codeine/APAP) and sum of pain intensity differences (3.8 for tramadol/APAP; 3.3 for codeine/APAP) were also comparable throughout. Overall assessments of efficacy by patients (mean score 2.9 in each treatment group) and investigators (mean score 3.0 for tramadol/APAP, 2.9 for codeine/APAP) were similar for the 2 treatment groups. Equivalent mean doses (3.5 tablets or capsules daily) and maximum daily doses (5.5 tablets or 5.7 capsules) were used in the 2 treatment groups. The overall incidence of adverse events was comparable, with a significantly higher proportion of patients in the codeine/APAP group reporting somnolence (24% [37/153] vs 17% [54/309], P = 0.05) or constipation (21% [32/153] vs 11% [35/309], P < 0.01) and a larger proportion of patients in the tramadol/APAP group reporting headache (11% [34/309] vs 7% [11/153], P = 0.08). CONCLUSION: The results of this study suggest that tramadol/APAP tablets (37.5 mg/325 mg) are as effective as codeine/ APAP capsules (30 mg/300 mg) in the treatment of chronic nonmalignant low back pain and OA pain and are better tolerated.

Intracardiac papillary fibroelastoma: an occult cause of embolic neurologic deficit.

We report the case of a young woman with a transient ischemic attack secondary to a rare intracardiac tumor, a papillary fibroelastoma. The tumor was identified by two-dimensional echocardiography and was treated surgically. The intracardiac papillary fibroelastoma as an uncommon source of occult cerebral emboli is discussed.

Treatment of refractory chronic demyelinating polyneuropathy with lymphoid irradiation.

Four patients with refractory or poorly responsive chronic progressive demyelinating polyneuropathy (CPDP) were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study. All patients had previously failed conventional therapy for CPDP, as well as other unconventional treatments. During a follow-up period of 7 to 12 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic subset) to Leu-3 (helper/inducer subset) T cells in the blood. Three of the four patients demonstrated improvement in distal muscle strength, and this was associated with increased functional capabilities in two patients. In contrast, no clinical improvement in sensation was noted in any patient. Nerve conduction studies showed patchy improvement in three patients. The results of this preliminary uncontrolled study indicate that radiotherapy deserves further study in the treatment of CPDP.

Brain infarction and hemorrhage in young and middle-aged adults.

Of 131 young (17 to 44 years) and middle-aged (45 to 55 years) adults who had brain infarction or hemorrhage, the most common etiologic factors were rheumatic heart disease, migraine and oral contraceptive use among the younger group. In contrast, atherosclerotic, hypertensive and diabetes-associated cerebrovascular were the most common causes in the middle-aged group. Patients who have a stroke before age 45 should have prompt, complete laboratory and radiologic testing to define a possible treatable cause.

Neurologic manifestations of podophyllin toxicity.

A young woman presented with podophyllin intoxication following topical application of podophyllin resin to genital condylomata acuminata. The disorder was marked by hallucinatory psychosis, bone marrow depression, and mild hepatic dysfunction. The psychosis and systemic disturbances resolved within 3 weeks, but were followed by autonomic and sensorimotor peripheral neuropathy. This case illustrates the transient central neurotoxicity and persistent peripheral neurotoxicity of podophyllin.

Plasma concentrations of phensuximide, methsuximide, and their metabolites in relation to clinical efficacy.

The clinical efficacy of phensuximide and methsuximide was studied in relation to plasma concentrations of these compounds and their desmethyl metabolites. Single- and chronic-dose studies of each drug were carried out in five patients with intractable seizures. Patients were evaluated before and during treatment by 6-hour simultaneous video and telemetered electroencephalographic recordings to characterize the seizure type and by daily determinations of plasma antiepileptic drug concentrations. Phensuximide had a mean half-life of 7.8 hours and accumulated to an average fasting level of only 5.7 micrograms per milliliter. Desmethylphensuximide averaged only 1.7 micrograms per milliliter with a similar half-life. Methsuximide had an even shorter half-life, averaging 1.4 hours, but its desmethyl metabolite had a mean half-life of 38 hours and therefore accumulated to levels in excess of 40 micrograms per milliliter. The addition of phensuximide to their regimens benefited none of the patients, but two had an excellent response to methsuximide. The failure of phensuximide and its desmethyl metabolite to accumulate to reasonable levels is the likely explanation for the relatively weak antiepileptic effect of phensuximide as compared with methsuximide.

Diagnostic and therapeutic reevaluation of patients with intractable epilepsy.

Intensive monitoring techniques were used to improve seizure diagnosis and control in 23 patients with intractable epilepsy: (1) Video recording of clinical seizures and the ictal EEG, (2) long-term telemetered EEG recordings, and (3) frequent determination of plasma antiepileptic drug concentrations. Patients were monitored in the hospital for an average of 8 weeks and after discharge were followed for an average of 8 months. At follow-up, 70 percent of the patients continued to have improved seizure control as compared with baseline studies, 83 percent had decreased toxicity, and about half had made gains in social adjustment. Use of the techniques described can make a significant contribution to patients previously considered intractable to therapy.